This revision of a proposal submitted initially on 10/1/06 requests three years of support (5/1/08-4/30/11) to investigate the onset, stability and remission in symptoms of nicotine dependence, the underlying risk and protective factors for different patterns for dependence, and the consequences of dependence over a four-year interval from late adolescence to early adulthood, in a crucial period of development for the acquisition of tobacco use behavior. The research has six major goals: (1) To identify patterns of initiation, stability and change in symptoms of nicotine dependence, and developmental trajectories of dependence symptoms from mid adolescence to early adulthood;(2) To identify the social, psychological and biological factors, within the Developmental Socialization framework, that promote (risk factors) and those that reduce (protective factors) dependence;(3) To identify the social, psychological and biological factors that predict persistence of dependence;(4) To identify the psychosocial and health consequences of nicotine dependence;(5) To specify the comorbidity, sequencing and reciprocal effects between nicotine dependence and depression and other psychiatric disorders;(6) In exploratory analyses, to identify differences by gender, race/ethnicity between non-Hispanic white, non-Hispanic African American and Hispanic youths, and age of tobacco use onset with respect to Aims (#1)-(#5). These aims will be achieved by conducting a new wave of data collection by telephone on a cohort of 1,036 adolescents, whom we last contacted in 2005 at mean age of 16.6 years (st. dev=1.3) and who will be 20.6 years on average when reinterviewed in 2009. These youths were previously interviewed five times over a two-year interval, from 2/2003 to 10/2005. This study represents a unique attempt to investigate prospectively the periods of risk for initiation and persistence of nicotine dependence in adolescence and early adulthood, the duration from onset to dependence, the factors that explain onset, chronicity and remission of dependence, the consequences of nicotine dependence, and the comorbidity among smoking, nicotine dependence, and psychiatric disorders among males and females and youths of different ethnicities. A crucial benefit of this additional wave of data collection is the update of phenotypes of nicotine dependence and other tobacco use behaviors for genetic analyses over a longer risk period than available to date. The study will generate a unique understanding of the natural history, etiology and consequences of nicotine dependence among young people. PUBLIC HEALTH RELEVANCE: Chronic smoking is one of the strongest contributors to morbidity and mortality in the population. This study proposes to identify the processes leading to nicotine dependence, its underlying risk and protective factors, and its consequences for physical health and psychosocial functioning in adolescence and early adulthood. These processes need to be studied beginning in adolescence since onset of tobacco use occurs in adolescence and early onset is associated with chronic use. The results will have important public health implications for the early diagnosis of nicotine dependence and the development of prevention, intervention and treatment efforts. The findings will indicate when, with whom, and how to intervene in order to prevent and reduce progression to nicotine dependence.